The purpose of this study is to gain new insights into the basic immunologic mechanisms involved in the initiation and amplification of acute and chronic inflamatory reactions in the lung. We shall study the pulmonary inflammatory processes following intratracheal instillation of purified complement components and their chemotactic fragments. Newly developed techniques for detection and quantitation of leukocytic influx into lungs (Indium111-PMN) and the established technique for detection of increase in vascular permeability (I125-Albumin) will be used. In addition, employing in vitro techniques, we plan to investigate inflammatory mediator induced modulation of synthesis of chemotactic factors and complement components by resident lung cells (alveolar macrophages and type II cells). Using newly developed methodology for radiolabeling of C3 and C5 we shall study the nature of fragmentation of these complement components by enzymes in lung constituents (bronchoalveolar cells and lavage fluid). We shall employ therapeutic reagents to study, identify, and inhibit these enzymes capable of generating phlogistic fragments of C3 and C5. The synthesis of complement components and generation of chemotactic fragment within the lung have the potential to initiate and perpetuate acute inflammation and induce structural damage to lung parenchyma. If uncontrolled, the continuous generation of proinflammatory factors such as C3 and C5 and their fragments has the potential to initiate chronic inflammation in the lung. By rigorous and careful exploration of the biochemical and immunopathological mechanisms of lung inflammation and injury induced by complement components and chemotactic factors generated by lung cells, we hope to gain new information that will have direct application to developing new diagnostic and therapeutic regimens for acute and chronic inflammatory lung disease in the human lung.